Christofidou-Solomidou Melpo, Pietrofesa Ralph A, Arguiri Evguenia, Schweitzer Kelly S, Berdyshev Evgeny V, McCarthy Maureen, Corbitt Astrid, Alwood Joshua S, Yu Yongjia, Globus Ruth K, Solomides Charalambos C, Ullrich Robert L, Petrache Irina
Department of Medicine, Pulmonary Allergy and Critical Care Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania;
Department of Medicine, Pulmonary and Critical Care Division, Indiana University School of Medicine, Indianapolis, Indiana;
Am J Physiol Lung Cell Mol Physiol. 2015 Mar 1;308(5):L416-28. doi: 10.1152/ajplung.00260.2014. Epub 2014 Dec 19.
Despite considerable progress in identifying health risks to crewmembers related to exposure to galactic/cosmic rays and solar particle events (SPE) during space travel, its long-term effects on the pulmonary system are unknown. We used a murine risk projection model to investigate the impact of exposure to space-relevant radiation (SR) on the lung. C3H mice were exposed to (137)Cs gamma rays, protons (acute, low-dose exposure mimicking the 1972 SPE), 600 MeV/u (56)Fe ions, or 350 MeV/u (28)Si ions at the NASA Space Radiation Laboratory at Brookhaven National Laboratory. Animals were irradiated at the age of 2.5 mo and evaluated 23.5 mo postirradiation, at 26 mo of age. Compared with age-matched nonirradiated mice, SR exposures led to significant air space enlargement and dose-dependent decreased systemic oxygenation levels. These were associated with late mild lung inflammation and prominent cellular injury, with significant oxidative stress and apoptosis (caspase-3 activation) in the lung parenchyma. SR, especially high-energy (56)Fe or (28)Si ions markedly decreased sphingosine-1-phosphate levels and Akt- and p38 MAPK phosphorylation, depleted anti-senescence sirtuin-1 and increased biochemical markers of autophagy. Exposure to SR caused dose-dependent, pronounced late lung pathological sequelae consistent with alveolar simplification and cellular signaling of increased injury and decreased repair. The associated systemic hypoxemia suggested that this previously uncharacterized space radiation-associated lung injury was functionally significant, indicating that further studies are needed to define the risk and to develop appropriate lung-protective countermeasures for manned deep space missions.
尽管在确定太空旅行期间机组人员暴露于银河/宇宙射线和太阳粒子事件(SPE)所面临的健康风险方面取得了相当大的进展,但其对肺部系统的长期影响仍不明确。我们使用小鼠风险预测模型来研究暴露于与太空相关辐射(SR)对肺部的影响。C3H小鼠在布鲁克海文国家实验室的美国国家航空航天局太空辐射实验室中接受了(137)Cs伽马射线、质子(急性、低剂量暴露,模拟1972年的SPE)、600 MeV/u的(56)Fe离子或350 MeV/u的(28)Si离子照射。动物在2.5月龄时接受辐照,并在辐照后23.5个月(即26月龄时)进行评估。与年龄匹配的未辐照小鼠相比,SR暴露导致气腔显著扩大和剂量依赖性的全身氧合水平降低。这些与晚期轻度肺部炎症和明显的细胞损伤相关,肺实质中存在显著的氧化应激和细胞凋亡(半胱天冬酶-3激活)。SR,尤其是高能(56)Fe或(28)Si离子显著降低了鞘氨醇-1-磷酸水平以及Akt和p38丝裂原活化蛋白激酶的磷酸化,消耗了抗衰老的沉默调节蛋白-1,并增加了自噬的生化标志物。暴露于SR会导致剂量依赖性的、明显的晚期肺部病理后遗症,与肺泡简化以及损伤增加和修复减少的细胞信号传导一致。相关的全身低氧血症表明,这种先前未被描述的与太空辐射相关的肺损伤在功能上具有重要意义,这表明需要进一步研究来确定风险,并为载人深空任务制定适当的肺部保护对策。